In this project, we propose to develop and apply sensitive methods for detecting low levels of residual neoplastic cells in several different bone marrow transplant settings. These methods will be used to study the fate of residual neoplastic cells and their potential clinical significance and prognostic importance. Polymerase chain reaction (PCR) techniques specific for chromosomal translocations and CDR3 sequences of rearranged immunoglobulin genes will be used to demonstrate the presence of leukemia and non-Hodgkin's lymphoma cells in marrow autografts at the time of purging and to assess the relative efficiency of various purging protocols for eradicating these cells. Similar techniques will be used to study the frequency and levels of subclinical leukemia and lymphoma cells following autologous and allogeneic marrow transplantation. Using a combination of two different molecular markers in a subset of patients, the relative utility of different PCR approaches for detecting minimal residual disease will be addressed. These studies will establish the prevalence of residual leukemia and lymphoma cells following bone marrow transplantation, their potential biological and clinical importance, and help define the technical limitations of various approaches for their molecular detection.